Description: (Applicant's Description) The long term objective of this Laboratory Program is the identification of compounds suitable for development as antitumor agents. During the project period, objectives include: (1) identifying mechanistically unique DNA damaging agents (2) obtaining more potent inhibitors of DNA polymerase beta so that it is possible to complete the testing of the hypothesis that these agents can potentiate the cytotoxic activity of antitumor agents that act by creating DNA lesions, and demonstrating the ability of such inhibitors to potentiate the antitumor activity of agents such as bleomycin, esperamicin and califcheamicin (3) fractionating prioritized extracts identified by Program 1 to isolate and structurally characterize the natural principle(s) (4) prioritizing the lead compounds identified by the studies outlined above and obtaining the most promising compounds in quantities sufficient for antitumor evaluation in experimental animal models/initial preclinical development.